{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:05:31Z","timestamp":1789751131789,"version":"4.0.1"},"reference-count":51,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["2025HXBH072"],"award-info":[{"award-number":["2025HXBH072"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82241086"],"award-info":[{"award-number":["82241086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273669"],"award-info":[{"award-number":["82273669"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574147"],"award-info":[{"award-number":["82574147"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Air pollution-induced cardiovascular disease is a leading contributor to the increasing global disease burden. Disruption of vascular endothelial function is a central driver of disease onset; however, the systemic mechanisms linking pollution exposure to endothelial dysfunction remain poorly defined. Here, we investigated early molecular responses to short-term exposure via integrated proteomic, metabolomic, and transcriptomic analyses. In a panel study of eight college students traveling from Qingdao to Shijiazhuang, China, where PM2.5, PM10, SO2, NO2, and CO levels were substantially higher, we collected serum samples at multiple time points and assessed endothelial responses via ex vivo biosensors. Proteomic profiling revealed the activation of hemostasis-related processes with interaction network analysis identifying F2 (prothrombin) as a central node strongly correlated with pollutant exposure. Metabolomic analysis revealed significant perturbations in bile acid biosynthesis and arginine\u2013proline metabolism, with PM2.5-associated metabolites predominantly enriched in energy metabolism-related pathways. Transcriptomic profiling of endothelial cells provided further corroborating evidence that acute exposure to ambient air pollutants is capable of triggering endothelial cell activation. Subsequent weighted gene coexpression network analysis identified F2 as a pivotal molecular mediator underlying air pollutant-induced endothelial dysfunction. Together, these findings delineate the molecular architecture of acute pollution-induced endothelial cell dysfunction and identify F2-centered pathways as potential early targets for mitigating cardiovascular toxicity.<\/jats:p>","DOI":"10.1021\/envhealth.5c00833","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T14:05:30Z","timestamp":1777298730000},"page":"1896-1909","source":"Crossref","is-referenced-by-count":0,"title":["Air Pollution\nExposure Induces Vascular Endothelial\nCell Dysfunction via Elevated Circulating F2: Multiomics Insights\nfrom an\n                    <i>Ex Vivo<\/i>\n                    Biosensor Assay"],"prefix":"10.1021","volume":"4","author":[{"given":"Jianzhong","family":"Zhang","sequence":"first","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]},{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Cheng","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]},{"name":"Sichuan University , , , ,","place":["Chengdu, Sichuan, China, 610041"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanting","family":"Li","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Sun","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Ma","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3962-0261","authenticated-orcid":true,"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hebei Medical University , , ,","place":["Shijiazhuang, China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9981-7966","authenticated-orcid":true,"given":"Jinglong","family":"Tang","sequence":"additional","affiliation":[{"name":"Qingdao University , , ,","place":["Qingdao, China, 266071"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"issue":"9","key":"2026091808061252600_cit1","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1136\/thoraxjnl-2013-204949","article-title":"The exposome:\na new paradigm to study the impact of environment on health","volume":"69","author":"Vrijheid","year":"2014","journal-title":"Thorax"},{"issue":"10082","key":"2026091808061252600_cit2","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1016\/S0140-6736(17)30505-6","article-title":"Estimates\nand 25-year\ntrends of the global burden of disease attributable to ambient air\npollution: an analysis of data from the Global Burden of Diseases\nStudy 2015","volume":"389","author":"Cohen","year":"2017","journal-title":"Lancet"},{"issue":"14","key":"2026091808061252600_cit3","doi-asserted-by":"publisher","first-page":"e800","DOI":"10.1161\/CIRCULATIONAHA.120.052666","article-title":"Taking a Stand\nAgainst Air Pollution-The Impact on Cardiovascular Disease: A Joint\nOpinion From the World Heart Federation, American College of Cardiology,\nAmerican Heart Association, and the European Society of Cardiology","volume":"143","author":"Brauer","year":"2021","journal-title":"Circulation"},{"key":"2026091808061252600_cit4","doi-asserted-by":"publisher","first-page":"1472996","DOI":"10.3389\/fmed.2024.1472996","article-title":"Effect of air pollution on the global\nburden of cardiovascular diseases and forecasting future trends of\nthe related metrics: a systematic analysis from the Global Burden\nof Disease Study 2021","volume":"11","author":"Mao","year":"2024","journal-title":"Front. 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Mater."},{"key":"2026091808061252600_cit29","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3389\/fmed.2018.00281","article-title":"Structure of Coagulation\nFactor II:\nMolecular Mechanism of Thrombin Generation and Development of Next-Generation\nAnticoagulants","volume":"5","author":"Chinnaraj","year":"2018","journal-title":"Front. Med."},{"issue":"3","key":"2026091808061252600_cit30","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1002\/rth2.12107","article-title":"Integrating\nplatelet and coagulation activation in fibrin clot formation","volume":"2","author":"Swieringa","year":"2018","journal-title":"Res. Pract. Thromb. Haemost."},{"issue":"1","key":"2026091808061252600_cit31","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1023\/A:1013952114485","article-title":"Receptors\nof the PAR family as a link between blood coagulation and inflammation","volume":"67","author":"Dugina","year":"2002","journal-title":"Biochemistry"},{"issue":"13","key":"2026091808061252600_cit32","doi-asserted-by":"publisher","first-page":"2760","DOI":"10.1182\/bloodadvances.2021004360","article-title":"A thrombin-PAR1\/2 feedback\nloop amplifies thromboinflammatory endothelial responses to the viral\nRNA analogue poly(I:C)","volume":"5","author":"Subramaniam","year":"2021","journal-title":"Blood Adv."},{"issue":"9","key":"2026091808061252600_cit33","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1182\/blood-2008-06-160135","article-title":"Effect\nof elevated levels of coagulation factors on the risk of venous thrombosis\nin long-distance travelers","volume":"113","author":"Kuipers","year":"2009","journal-title":"Blood"},{"issue":"4","key":"2026091808061252600_cit34","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.3892\/mmr.2017.6217","article-title":"A genetic risk factor for thrombophilia\nin a Han Chinese family","volume":"15","author":"Sun","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"2026091808061252600_cit35","doi-asserted-by":"publisher","first-page":"100233","DOI":"10.1016\/j.tru.2026.100233","article-title":"Prothrombin\nconcentrations in middle-aged men and women \u2013 stability over\ntime and correlations with cardiovascular risk factors","volume":"22","author":"Zo\u0308ller","year":"2026","journal-title":"Thromb. Update"},{"issue":"8","key":"2026091808061252600_cit36","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1093\/cvr\/cvad046","article-title":"Post-transcriptional\ncontrol of haemostatic genes: mechanisms and emerging therapeutic\nconcepts in thrombo-inflammatory disorders","volume":"119","author":"Danckwardt","year":"2023","journal-title":"Cardiovasc. Res."},{"issue":"3","key":"2026091808061252600_cit37","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.molcel.2010.12.032","article-title":"p38 MAPK controls prothrombin expression\nby regulated RNA 3\u2032 end processing","volume":"41","author":"Danckwardt","year":"2011","journal-title":"Mol.\nCell"},{"issue":"8","key":"2026091808061252600_cit38","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3390\/toxics12080587","article-title":"Cross-Omics Analyses Reveal the Effects\nof Ambient PM(2.5) Exposure on Hepatic Metabolism in Female Mice","volume":"12","author":"Yan","year":"2024","journal-title":"Toxics"},{"key":"2026091808061252600_cit39","doi-asserted-by":"publisher","first-page":"153850","DOI":"10.1016\/j.tox.2024.153850","article-title":"Fine particulate\nmatter disrupts bile acid homeostasis\nin hepatocytes via binding to and activating farnesoid X receptor","volume":"506","author":"Zhang","year":"2024","journal-title":"Toxicology"},{"issue":"1","key":"2026091808061252600_cit40","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13045-023-01453-1","article-title":"Amino acid\nmetabolism in immune cells: essential regulators of the effector functions,\nand promising opportunities to enhance cancer immunotherapy","volume":"16","author":"Yang","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"2026091808061252600_cit41","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.envint.2019.04.003","article-title":"Perturbations\nof the arginine metabolome following\nexposures to traffic-related air pollution in a panel of commuters\nwith and without asthma","volume":"127","author":"Liang","year":"2019","journal-title":"Environ. Int."},{"issue":"Pt B","key":"2026091808061252600_cit42","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/j.envpol.2018.09.062","article-title":"Air pollution-derived\nPM(2.5) impairs mitochondrial function in healthy and chronic obstructive\npulmonary diseased human bronchial epithelial cells","volume":"243","author":"Leclercq","year":"2018","journal-title":"Environ. Pollut."},{"issue":"6","key":"2026091808061252600_cit43","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/s12012-022-09737-7","article-title":"PM(2.5) Exposure Lowers Mitochondrial\nEndurance During\nCardiac Recovery in a Rat Model of Myocardial Infarction","volume":"22","author":"Sivakumar","year":"2022","journal-title":"Cardiovasc. Toxicol."},{"key":"2026091808061252600_cit44","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.tiv.2016.02.001","article-title":"Particulate matter induces\nprothrombotic microparticle shedding by human mononuclear and endothelial\ncells","volume":"32","author":"Neri","year":"2016","journal-title":"Toxicol. In Vitro"},{"issue":"2","key":"2026091808061252600_cit45","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1160\/TH17-05-0362","article-title":"Urban Particulate\nMatter Induces Changes in Gene Expression in Vascular Endothelial\nCells that Are Associated with Altered Clot Structure In Vitro","volume":"118","author":"Pan","year":"2018","journal-title":"Thromb. Haemost."},{"issue":"2","key":"2026091808061252600_cit46","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1093\/jb\/117.2.244","article-title":"Activation of prothrombin\nby factor Xa bound to the membrane surface of human umbilical vein\nendothelial cells: its catalytic efficiency is similar to that of\nprothrombinase complex on platelets","volume":"117","author":"Sugo","year":"1995","journal-title":"J. Biochem."},{"issue":"8","key":"2026091808061252600_cit47","doi-asserted-by":"publisher","first-page":"3008","DOI":"10.1182\/blood-2002-08-2527","article-title":"Elevated prothrombin\nresults in clots with an altered fiber structure: a possible mechanism\nof the increased thrombotic risk","volume":"101","author":"Wolberg","year":"2003","journal-title":"Blood"},{"issue":"5","key":"2026091808061252600_cit48","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1160\/th14-02-0167","article-title":"Protease-activated\nreceptor signalling by coagulation proteases in endothelial cells","volume":"112","author":"Rezaie","year":"2014","journal-title":"Thromb. 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